Process Development of Febuxostat Using Palladium- and Copper-Catalyzed C–H Arylation

There is significant interest in the development of process routes for active pharmaceutical ingredients using C–H arylation methodology. An efficient and practical synthetic route for febuxostat (1), which is the first non-purine-type xanthine oxidase inhibitor, was established via palladium- and copper-catalyzed C–H arylation of thiazole with aryl bromide. The catalyst loading was reduced to 0.1 mol % for the intermolecular C–H arylation, and a three-step synthesis produced febuxostat in 89% overall yield with excellent selectivity.